Positive selection of apoptosis-resistant cells correlates with activation of dominant-negative STAT5

Chiara Bovolenta, Lucia Testolin, Luisa Benussi, Patricia M J Lievens, Elio Liboi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The STAT5 activation has important roles in cell differentiation, cell cycle control, and development. However, the potential implications of STAT5 in the control of apoptosis remain unexplored. To evaluate any possible link between the erythropoietin receptor (EpoR) JAK2/STAT5 transduction pathway and apoptosis, we have investigated apoptosis, resistant cells (ApoR) that arose from positive selection of the erythroid-committed Ba/F3EpoR cells triggered to apoptosis by ectopic expression of the HOX-B8 homeotic gene. We show that JAK2 is normally activated by Epo in both Ba/F3EpoR and ApoR cells. In contrast, both STAT5a and STAT5b isoforms are uniquely activated in a C- truncated form (86 kDa) only in ApoR cells. Analysis of ApoR and Ba/F3EpoR subclones confirmed that the switch to the truncated STAT5 isoform coincides with apoptosis survival and that ApoR do not derive from preexisting cells with a shortened STAT5. In addition, ApoR cells die in the absence of Epo. This indicates that resistance to apoptosis is not because of a general defect in the apoptotic pathway of ApoR cells. Furthermore, we show that the 86-kDa STAT5 protein presents a dominant-negative (DN) character. We hypothesize that the switch to aDN STAT5 may be part of a mechanism that allows ApoR cells to be selectively advantaged during apoptosis. In conclusion, we provide evidence for a functional correlation between a naturally occurring DN STAT5 and a biological response.

Original languageEnglish
Pages (from-to)20779-20784
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number33
DOIs
Publication statusPublished - Aug 14 1998

Fingerprint

Chemical activation
Apoptosis
Protein Isoforms
Switches
STAT5 Transcription Factor
Erythropoietin Receptors
Homeobox Genes
Cell Cycle Checkpoints
Cell Differentiation
Genes
Cells
Defects

ASJC Scopus subject areas

  • Biochemistry

Cite this

Positive selection of apoptosis-resistant cells correlates with activation of dominant-negative STAT5. / Bovolenta, Chiara; Testolin, Lucia; Benussi, Luisa; Lievens, Patricia M J; Liboi, Elio.

In: Journal of Biological Chemistry, Vol. 273, No. 33, 14.08.1998, p. 20779-20784.

Research output: Contribution to journalArticle

Bovolenta, Chiara ; Testolin, Lucia ; Benussi, Luisa ; Lievens, Patricia M J ; Liboi, Elio. / Positive selection of apoptosis-resistant cells correlates with activation of dominant-negative STAT5. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 33. pp. 20779-20784.
@article{6fa5d30ab0914e96b7bcb7cfadd05ce6,
title = "Positive selection of apoptosis-resistant cells correlates with activation of dominant-negative STAT5",
abstract = "The STAT5 activation has important roles in cell differentiation, cell cycle control, and development. However, the potential implications of STAT5 in the control of apoptosis remain unexplored. To evaluate any possible link between the erythropoietin receptor (EpoR) JAK2/STAT5 transduction pathway and apoptosis, we have investigated apoptosis, resistant cells (ApoR) that arose from positive selection of the erythroid-committed Ba/F3EpoR cells triggered to apoptosis by ectopic expression of the HOX-B8 homeotic gene. We show that JAK2 is normally activated by Epo in both Ba/F3EpoR and ApoR cells. In contrast, both STAT5a and STAT5b isoforms are uniquely activated in a C- truncated form (86 kDa) only in ApoR cells. Analysis of ApoR and Ba/F3EpoR subclones confirmed that the switch to the truncated STAT5 isoform coincides with apoptosis survival and that ApoR do not derive from preexisting cells with a shortened STAT5. In addition, ApoR cells die in the absence of Epo. This indicates that resistance to apoptosis is not because of a general defect in the apoptotic pathway of ApoR cells. Furthermore, we show that the 86-kDa STAT5 protein presents a dominant-negative (DN) character. We hypothesize that the switch to aDN STAT5 may be part of a mechanism that allows ApoR cells to be selectively advantaged during apoptosis. In conclusion, we provide evidence for a functional correlation between a naturally occurring DN STAT5 and a biological response.",
author = "Chiara Bovolenta and Lucia Testolin and Luisa Benussi and Lievens, {Patricia M J} and Elio Liboi",
year = "1998",
month = "8",
day = "14",
doi = "10.1074/jbc.273.33.20779",
language = "English",
volume = "273",
pages = "20779--20784",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "33",

}

TY - JOUR

T1 - Positive selection of apoptosis-resistant cells correlates with activation of dominant-negative STAT5

AU - Bovolenta, Chiara

AU - Testolin, Lucia

AU - Benussi, Luisa

AU - Lievens, Patricia M J

AU - Liboi, Elio

PY - 1998/8/14

Y1 - 1998/8/14

N2 - The STAT5 activation has important roles in cell differentiation, cell cycle control, and development. However, the potential implications of STAT5 in the control of apoptosis remain unexplored. To evaluate any possible link between the erythropoietin receptor (EpoR) JAK2/STAT5 transduction pathway and apoptosis, we have investigated apoptosis, resistant cells (ApoR) that arose from positive selection of the erythroid-committed Ba/F3EpoR cells triggered to apoptosis by ectopic expression of the HOX-B8 homeotic gene. We show that JAK2 is normally activated by Epo in both Ba/F3EpoR and ApoR cells. In contrast, both STAT5a and STAT5b isoforms are uniquely activated in a C- truncated form (86 kDa) only in ApoR cells. Analysis of ApoR and Ba/F3EpoR subclones confirmed that the switch to the truncated STAT5 isoform coincides with apoptosis survival and that ApoR do not derive from preexisting cells with a shortened STAT5. In addition, ApoR cells die in the absence of Epo. This indicates that resistance to apoptosis is not because of a general defect in the apoptotic pathway of ApoR cells. Furthermore, we show that the 86-kDa STAT5 protein presents a dominant-negative (DN) character. We hypothesize that the switch to aDN STAT5 may be part of a mechanism that allows ApoR cells to be selectively advantaged during apoptosis. In conclusion, we provide evidence for a functional correlation between a naturally occurring DN STAT5 and a biological response.

AB - The STAT5 activation has important roles in cell differentiation, cell cycle control, and development. However, the potential implications of STAT5 in the control of apoptosis remain unexplored. To evaluate any possible link between the erythropoietin receptor (EpoR) JAK2/STAT5 transduction pathway and apoptosis, we have investigated apoptosis, resistant cells (ApoR) that arose from positive selection of the erythroid-committed Ba/F3EpoR cells triggered to apoptosis by ectopic expression of the HOX-B8 homeotic gene. We show that JAK2 is normally activated by Epo in both Ba/F3EpoR and ApoR cells. In contrast, both STAT5a and STAT5b isoforms are uniquely activated in a C- truncated form (86 kDa) only in ApoR cells. Analysis of ApoR and Ba/F3EpoR subclones confirmed that the switch to the truncated STAT5 isoform coincides with apoptosis survival and that ApoR do not derive from preexisting cells with a shortened STAT5. In addition, ApoR cells die in the absence of Epo. This indicates that resistance to apoptosis is not because of a general defect in the apoptotic pathway of ApoR cells. Furthermore, we show that the 86-kDa STAT5 protein presents a dominant-negative (DN) character. We hypothesize that the switch to aDN STAT5 may be part of a mechanism that allows ApoR cells to be selectively advantaged during apoptosis. In conclusion, we provide evidence for a functional correlation between a naturally occurring DN STAT5 and a biological response.

UR - http://www.scopus.com/inward/record.url?scp=0032516816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032516816&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.33.20779

DO - 10.1074/jbc.273.33.20779

M3 - Article

C2 - 9694822

AN - SCOPUS:0032516816

VL - 273

SP - 20779

EP - 20784

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 33

ER -